Researchers at the University of California, Riverside found that chronic consumption of a western diet leads to overeating and obesity due to elevations in "peripheral endocannabinoid signalling."
The endocannabinoid system is located throughout the mammalian body, including the brain and all peripheral organs, and participates in the control of many physiological functions in the body, including food intake, energy balance, and reward.
It is comprised of lipid signalling molecules called endocannabinoids - which can be thought of as the body's own "natural cannabis" - that bind to cannabinoid receptors located on cells throughout the body.
"This therapeutic approach to targeting the periphery has substantial advantages over traditional drugs that interact with the brain and cause psychiatric side-effects," said DiPatrizio.
The work describes for the first time that overeating associated with chronic consumption of a western diet is driven by an enhancement in endocannabinoid signals generated in peripheral organs, researchers said.
To examine the role for endocannabinoids generated in peripheral organs in controlling the overeating of western diet, DiPatrizio and Donovan A Argueta, a bioengineering PhD student in his lab, used a mouse model of western diet-induced obesity (chronic exposure to high levels of sugars and fats).
"These hyperphagic responses to western diet were met with greatly elevated levels of endocannabinoids in the small intestine and circulation," DiPatrizio said.
"We found blocking the actions of the endocannabinoids with pharmacological inhibitors of cannabinoid receptors in the periphery completely normalised food intake and meal patterns in western diet-induced obese mice to levels found in control lean mice fed standard chow," he said.
"Importantly, however, other research groups have reported elevations in circulating levels of endocannabinoids in obese human subjects, which suggests that this system may also be overactive in human obesity," DiPatrizio said.
The study appears in the journal Physiology and Behaviour.
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